The Minor Receptor Group of Human Rhinovirus (HRV) Includes HRV23 and HRV25, but the Presence of a Lysine in the VP1 HI Loop Is Not Sufficient for Receptor Binding

Abstract

Like all 10 minor receptor group human rhinoviruses (HRVs), HRV23 and HRV25, previously classified as major group viruses, are neutralized by maltose binding protein (MBP)-V33333 (a soluble recombinant concatemer of five copies of repeat 3 of the very-low-density lipoprotein receptor fused to MBP), bind to low-density lipoprotein receptor in virus overlay blots, and replicate in intercellular adhesion molecule 1 (ICAM-1)-negative COS-7 cells. From phylogenetic analysis of capsid protein VP1-coding sequences, they are also known to cluster together with other minor group strains. Therefore, they belong to the minor group; there are now 12 minor group and 87 major group HRV serotypes. Sequence comparison of the VP1 capsid proteins of all HRVs revealed that the lysine in the HI loop, strictly conserved in the 12 minor group HRVs, is also present in 9 major group serotypes that are neutralized by soluble ICAM-1. Despite the presence of this lysine, they are not neutralized by MBP-V33333 and fail to replicate in COS-7 cells and in HeLa cells in the presence of an ICAM-1-blocking antibody. These nine serotypes are therefore "true" major group viruses.Human rhinoviruses (HRVs), the main causative agents of common cold, were originally classified as acid-sensitive picornaviruses (34). Later, based on competition for cellular binding sites, two different groups of viruses using nonidentical receptors for cell attachment were defined within the genus Rhinovirus (18). Subsequently, 24 (1) and finally 100 serotypes (counting the subtypes HRV1A and HRV1B as one strain) were assigned to the two receptor groups by using cross-competition and inhibition of cell binding by a monoclonal antibody recognizing intercellular adhesion molecule 1 (ICAM-1), the receptor of the major group of HRVs (32,33,35). According to these reports, 90 serotypes bind ICAM-1, whereas both subtypes of HRV1 (HRV1A and HRV1B) and 8 other serotypes were categorized as belonging to the minor group; they were later shown to use members of the low-density-lipoprotein receptor (LDLR) family for cell entry (12,20,36). HRV87 was noted to be an exception in that it binds a sialylated membrane protein. Based on comparison of nucleotide sequences in several genomic regions, HRV87 was subsequently classified as an acid-sensitive enterovirus and found to be a prime strain of enterovirus 68 that uses decay-accelerating factor as a receptor (2,27). By phylogenetic analysis of capsid protein VP4/VP2 coding sequences of all HRV prototype strains, 74 HRV serotypes, including all the minor receptor group ones, were classified as HRV species A, while the 25 remaining serotypes form HRV species B (27). In a paper from the Colonno group, primary data on the competition with an ICAM-1-blocking antibody were not explicitly presented for all serotypes, in particular not for HRV23 and HRV25, and the presumed allocation of all HRVs to either group was depicted only in the form of a summarizing figure (35). Despite this, it was generally accepted that 90 serotypes, including HRV23...

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

“…The conservation of the 'minor receptor group-like' residues in the ICAM-1 footprint of the major receptor group HRV predicts that these HRV field strains have not evolved to use the major receptor ICAM-1. It has been shown previously that the lysine (Lys) 1224 in the HI loop of VP1 is strictly conserved in all minor receptor group HRV prototypes (Laine et al, 2005;Ledford et al, 2004;Vlasak et al, 2003) and is believed to be essential but not sufficient for HRV attachment to members of the LDLR family (Vlasak et al, 2005b). This Lys was also conserved in 24 of 28 HRV field strains characterized in this study, but was substituted with arginine (Arg) in the remaining four HRV strains.…”

“…Twelve HRV-A serotypes (HRV1A, 1B, 2, 23, 25, 29, 30, 31, 44, 47, 49 and 62), the minor receptor group, use members of the lowdensity lipoprotein receptor (LDLR) family, which are proposed to bind their ligands by electrostatic interactions with negatively charged ligand-binding domains (Gruenberger et al, 1995;Hofer et al, 1994;Marlovits et al, 1998;Vlasak et al, 2005b). The cellular receptor for the remaining HRV-A serotypes and all the HRV-B viruses (the major receptor group) is a cell surface member of the immunoglobulin supergene family called intercellular adhesion molecule 1 (ICAM-1) (Greve et al, 1989; Staunton et al, 1989; Tomassini et al, 1989).…”

Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation

“…They were selected to belong to different species and different receptor groups: HRV89 is a major group genus A; HRV3, HRV14, HRV37 and HRV72 are major group genus B; HRV18 and 54 are K-types (i.e. major group HRVs possessing a lysine in the HI loop of VP1) [40] and HRV1A, HRV29 and 44 are minor group genus A. Both the anti-89VP1 and anti-14VP1 antibodies inhibited infection of HeLa cells by half of these HRV serotypes in a concentration-dependent manner independent of their evolutionary relationship ( fig.…”

Induction of Autophagy Does Not Affect Human Rhinovirus Type 2 Production

“…As picornaviruses, they are nonenveloped, with a positive-sense RNA genome (12). Of the 99 HRV serotypes, 12 (the minor group) use members of the low-density lipoprotein receptor family and 87 (the major group) use intercellular adhesion molecule 1 for cell entry (13). The prototype minor-group virus HRV2 is internalized and routed to late endosomes, where RNA uncoating occurs (2,9).…”